The treatment of severe chronic pain which may be idiopathic or result from diseases such as cancer, rheumatism and arthritis is central to the treatment of these conditions. The range of pain felt by e.g., tumor patients comprises pain of the periosteum and of the bone itself as well as visceral pain and pain in soft tissues.
All chronic severe pain forms render the daily life of patients intolerable and often lead to depressive states. Successful pain therapy resulting in a lasting improvement of quality of life for the patients is therefore equally important to the success of a comprehensive therapy as is the treatment of the actual causes of the disease.
It has become accepted practice to use strong analgesics such as opioids for treating chronic severe pain for cancer patients as well as for patients which experience pain for other reasons.
Typically chronic pain patients are titrated with strong analgesics such as opioids in order to find a suitable dose range for a specific opioid such as e.g., morphine or oxycodone. Once a dosage amount being suitable to permanently control the chronic pain experience of these patients has been identified, the medication is taken on a by-the-clock-regimen which means that a certain dose will be taken e.g., every 8 hours, every 12 hours or only once a day. Such patients which without pain treatment would suffer from chronic pain sensation are typically designated as patients with a controlled background pain.
In order to achieve a constant control of background pain, patients will usually administer so-called controlled release or sustained release preparations of the analgesic in question. Sustained release preparations particularly of opioids are well-known in e.g., in the form of the tablets “MST-Continus”, “Palladon” and “Oxygesic” (all marketed by Mundipharma GmbH, Germany). These sustained release dosage forms are characterized in that they release the active agent over a prolonged period of time which allows the frequency of administration of these preparations to be reduced. This in turn has a number of important advantages for the patient because the patient for example can sleep through a constant period of 6 to 8 hours. Furthermore, the reduced frequency of administration often leads to increased patient compliance with medication.
Even though a lot of cancer patients are nowadays treated with opioids efficiently and can be considered to have controlled background pain, they experience from time to time a transitory increase in pain to greater than the usual moderate intensity.
This flare-up of moderate to severe pain that “breaks through” despite a by-the-clock analgesic regimen for treatment of chronic pain is typically described at breakthrough pain (BTP). The term breakthrough pain has become accepted in the lexicon of chronic pain treatment specialists and thus refers generally to a transitory exacerbation of pain that occurs on a background of otherwise stable controlled pain in a patient receiving analgesic therapy (see e.g., Portenoy et al (1990), Pain, 41:273-281, Cara et al (2004), Pain, 108:17-27, Portenoy et al (1999), Pain, 81:129-134 and Portenoy et al (2006) The Journal of Pain, 7(8):583-591). The phenomenon of breakthrough pain has also been labelled as “incident pain” and “episodic pain”.
In studies of cancer populations, 50 to 90% of patients with chronic pain experience breakthrough pain attacks which have also been reported in opioid-treated patients with chronic non-cancer pain (see Portenoy et al (2006), The Journal of Pain, 7(8):583-591).
Thus, even though treatment of pain, regardless of its origin, with strong analgesics as opioids nowadays does not encounter the same prejudices by medical practitioners as in the past, a well-titrated patient which is on a continuous opioid dosage regimen may still suffer from annoying and painful attacks. Clearly there is a strong need to account for the breakthrough pain phenomenon and different attempts have been made in the prior art to render the life of these patients which suffer from sudden pain attacks more comfortable.
For treating breakthrough pain a patient will typically receive an additional amount of a strong analgesic such as the opioid which he constantly takes for controlling the background pain.
As breakthrough pain attacks occur usually suddenly and need to be treated on a short time scale, these additional analgesic dosage amounts will usually be provided in the form of a fast acting preparation. In case of opioids one may therefore administer the additional dosage either parenteral, which would give an immediate onset of action, or alternatively administer oral immediate release preparations of opioids such as e.g., morphine and oxycodone.
Oral immediate release dosage forms may take the form of liquids or immediate release tablets.
In view of the recognition that breakthrough pain represents a significant clinical problem, such “rescue medication” has become widely accepted for treating pain.
However, as short acting opioid formulations are typically used for treating breakthrough pain attacks on an “as needed” basis in patients which already take a fixed scheduled opioid regimen, one has to take care that a patient is not overdosed. Additionally short acting opioid formulations such as liquids that are either to be taken by the oral route or administered parenterally, are notoriously prone to abuse by individuals that do not attempt to take the medication for treating pain but rather will try to isolate the opioids thereof and to use them for illicit recreational purposes.
Given the possibility that exposure to short-acting opioid formulations might increase the risk of abuse among the sub-population pre-deposed to abuse or addiction it is prudent to implement rescue dosing on a case by case basis after a careful assessment of risks and benefits. This typically leads to the situation that patients suffering form breakthrough pain receive the necessary short acting medication only under supervision of a medical practitioner which, of course severely impairs the freedom of such patients to move and to take the required medicine at any location and point in time. Parenteral administration of short acting opioids also severely suffers from the low acceptance of administering a medication by a needle device.
Moreover, it was found that patients on oral dosing find that the onset of action of an oral dose is sometimes too slow to experience rescue and therefore typically better results in treating breakthrough pain attacks are achieved with parenteral “rescue” medication.
Thus, there is a strong need in the art to provide a pharmaceutical composition that allows treatment of breakthrough pain and which can be taken by a patient as needed without supervision of medical practitioners at any time. At the same time these pharmaceutical compositions should be less prone to abuse as are the fast acting opioid formulations that are commonly used for treating breakthrough pain attacks.